【持续性肾脏替代治疗crrt英文精品课件】prevention and treatment of acute renal failure in sepsis

PreventionandTreatmentofAcuteRenalFailureinSepsisANS DEVRIESEJAmSocNephrol14 792 805 2003 Supervisor 主治醫師李博仁Reporter 住院醫師巫文平VGHTC 9211 Introduction ARF Commoncomplicationofsepsisandcarriesanominousprognosis MortalityofARF SepticARF 74 5 ARFnotrelatedtosepsis 45 2 ARF Increasesmorbidityandmortalityofsepsis PreventionandTreatmentofAcuteRenalFailureinSepsis TreatmentwithFluids Vasopressors andDiureticsSpecificPharmacologicTreatmentDialyticTreatmentConclusion TreatmentwithFluids Vasopressors andDiuretics VolumeExpansionVasopressorsLow DoseDopamineDiuretics I VolumeExpansion OptimizationofsystemichemodynamicsandeffectiveintravascularvolumeimportanttopreventARFinptswithsepsis Whatconstitutesoptimalhemodynamicsremainslargelyundefined I VolumeExpansion 3systematicreviewsofrandomizedcontrolledtrialscomparingcrystalloidswithcolloidsyieldedconflictingresults Thenatureandtargetsofanoptimalfluidresuscitationregimencontinuetobeanunresolvedissue II Vasopressors WhenappropriatevolumeexpansionfailstorestoreBPinptswithsepsis vasopressorsareindicated PhysicianshavebeenconcernedabouttheiruseforfearthatintrarenalvasoconstrictionwouldabrogatethebenefitsofincreasedBP Norepinephrine Inaptwithsepsis characterizedbysystemicvasodilatationandimpairedrenalautoregulation NorepinephrineadministrationmaybeexpectedtoimproveRBF Severalnon controlledstudiesinptswithsepsisNorepinephrineaugmentedurineoutput GFRAprospectiveobservationalstudyin97ptswithsepticshocklowermortalityinptstreatedwithnorepinephrinethanthosewithothervasopressorsmainlyhigh dosedopamine Vasopressin Vasopressin ahormonesecretedbytheposteriorpituitary increasessystemicvascularresistancethroughactivationofV1a receptorsonvascularsmoothmusclecells Arandomizedtrialin24ptswithsepticshockdemonstratedthata4 hinfusionofargininevasopressinImprovedurineoutput creatinineclearancewithsimilareffectsonBPandcardiacoutput ascomparedwithnorepinephrine II Vasopressors VasopressorscanbeusedsafelytorestoreBPwithoutcompromisingrenalfunctioninpatientswithsepticshock Norepinephrineispreferabletodopamine Inpatientsrefractorytonorepinephrine earlyuseofargininevasopressinisrecommended III Low DoseDopamine Low dosedopamine 1to3 g kg min increasesRBF diuresis andnatriuresisinhealthyanimals humansmaybeofpotentialbenefitinptswithARF SideeffectofDopamine DepressrespiratorydriveTriggertachyarrhythmias myocardialischemia Suppressallanteriorpituitary dependenthormones exceptforcortisoldecreaseTcellfunction III Low DoseDopamine Low dosedopamineindifferentmodelsofexperimentalARF includingischemicARFandsepticemia protectiveornobeneficialeffectsLow dosedopamineforrenoprotectivepurposesshouldbeabandoned duetoNoevidencesupportingitseffectivenessPrecipitateseriouscardiovascular metaboliccomplicationsincriticallyillpts IV Diuretics Intravascularvolumedepletionshouldbecarefullycorrectedasanalreadydamagedkidneymaybeprofoundlyinjuredbyarelativelymilddecreaseinperfusionpressure Inptswithsustainedoliguriadespitehighdosesofloopdiuretics treatmentshouldbewithdrawn Inresponders continuousinfusionsarepreferred moreeffective associatedwithlesstoxicity SpecificPharmacologicTreatment Anti TNF TherapyInhibitionofPlatelet ActivatingFactorInhibitionofNitricOxideSynthaseEndothelinAntagonismInhibitorsofArachidonicAcidMetabolismNatriureticPeptidesInhibitionofLeukocyteAdhesionInhibitorsofCoagulation ActivateproteinCGrowthFactors Anti TNF Therapy TNF affectsthekidneyIndirect inducinghypotensionandreleasinginflammatorymediatorsinthecirculationDirect TNF mediatedrenaldamageinsepsis Successofanti TNFtherapiesinanimalmodelswithpreventionofbothmortalityandRFthebutnotinhumansAmoreprofoundknowledgeofcytokineprofilesinsepticemiabetterselectionofptsthatwillmostlikelybenefitfromthesetherapies InhibitionofPlatelet ActivatingFactor AlargephaseIIItrialwithPAFacetylhydrolase arecombinantformoftheendogenoushumanenzymethathydrolyzesPAF hasbeeninitiatedinptswithseveresepsis Althoughexperimentalstudiesareencouraging nofirmconclusionsonthevalueofPAFantagonisminsepticARFcanbedrawnintheabsenceofinformationfromclinicaltrials InhibitionofNitricOxideSynthase TheubiquitousnatureandthepleiotropiceffectsoftheNOsystem itscomplexalterationsinsepsisandARF explainwhyNOSinhibitionfailstoshowlaudableeffects NO essentialtocounterbalancethevasoconstrictonandmaintainRBF inhibitinfiltrationofleukocytes topreventthrombosis ExcessiveNOproduction Exacerbatestheinjuriouseffectsofischemiaontubularcells EndothelinAntagonism EffectiveinexperimentalmodelsofsepsisAnonselectiveETantagonistincreasedtheriskofcontrastnephropathyinpatientswithchronicrenalfailureundergoingcoronaryangiography ThemixedresultsinexperimentalmodelsofsepsisandthedeleteriouseffectsinhumancontrastnephropathyReexaminetherationaleforETantagonismbeforeembarkingonclinicaltrialsinpatientswithARFandsepsis InhibitorsofArachidonicAcidMetabolism Inptswithsepsis cyclooxygenaseinhibitionwithibuprofenReducedthesynthesisofthromboxaneandprostacyclin NoeffectonthedevelopmentofshockorrenalfailureNoimprovementofsurvival Clinicalstudieswithselectivethromboxaneorleukotrieneinhibitorshavenotbeenperformed NatriureticPeptides Inanoncontrolledstudyof11ptswhodevelopedARFaftercardiacsurgery long term 48 h ANPinfusionimprovedRBFandGFRIn3randomizedplacebo controlledtrialsincriticallyillptswithARF ainfusionofANP anaritideorurodilatine didnotimproverenalfunctionNoconvincingevidencetosupporttheuseofnatriureticpeptidesasadjunctivetreatmentinARF InhibitionofLeukocyteAdhesion InhibitionofleukocyterecruitmentisapotentialpromisingapproachinthetreatmentofsepticARF butdatainhumansarerequiredbeforerelevantconclusionscanbedrawn InhibitorsofCoagulation Rationale DICiscommoninsepticptsandisassociatedwithanadverseprognosis Itischaracterizedbyageneralizedactivationofthecoagulationcascade resultingintheintravascularformationoffibrinclots endothelialdamage Impairedtissuebloodsupplycontributestoorgandysfunction includingARF InhibitorsofCoagulation Rationale TissueFactorPathwayInhibitor tissuefactorinhibitedbyanaturalanticoagulant tissuefactorpathwayinhibitor TFPI Antithrombin blocksseveralproteasesinvolvedincoagulation butitsinhibitoryeffectismostpowerfulagainstfactorXaandthrombinPlasmalevelsofantithrombinareusuallymarkedlyreducedinptswithsepsis whichisassociatedwithanincreasedmortalityActivatedProteinC ActivatedProteinC ProteinCisactivatedbythethrombin thrombomodulincomplexonendothelialcells ActivatedproteinCinhibitsthrombingenerationbyinactivatingfactorVaandfactorVIIIa ActivatedproteinChasdirectantiinflammatoryproperties includingimpairmentofleukocyteadhesiontotheendotheliumbybindingselectinsandinhibitionoftheproductionofinflammatorycytokinesbymonocytes Itstimulatesthefibrinolyticresponsebyinhibitingplasminogen activatorinhibitortype1 ProposedActionsofActivatedProteinCinModulatingtheSystemicInflammatory Procoagulant andFibrinolyticHostResponsestoInfection NEnglJMed Vol 344 No 10 March8 2001TAFI thrombin activatablefibrinolysisinhibitor PAI 1 plasminogen activatorinhibitor1 ActivatedProteinC Inarandomized multicentertrialconductedin1690ptswithseveresepsis recombinanthumanactivatedproteinCsignificantlyreducedmortality Treatmentwithdrotrecoginalfaactivated 24 g kgofbodyweight hourforatotaldurationof96hours Reducesmortalityinptswithseveresepsis Increasesriskofbleeding Moreefficacy intheseriouslyillpts asassessedbytheAPACHEIIscore thenumberoffailingorgans thepresenceofshock Kaplan MeierEstimatesofSurvivalamong850PatientswithSevereSepsisintheDrotrecoginAlfaActivatedGroupand840PatientswithSevereSepsisinthePlaceboGroup InhibitorsofCoagulation Conclusion SeveralstrategiestoinhibitcoagulationhavebeenevaluatedasadjunctivetherapiesinsepsisonlyactivatedproteinChasprovedsuccessful ThesuccessofactivatedproteinCmayhingeonitscombinedeffectsoncoagulation fibrinolysis inflammation ratherthananticoagulationalone ActivatedproteinCiscurrentlythefirstbiologicagentapprovedbytheFDAforthetreatmentofsepsis TheFDAhasrestricteditsusetoptswithanAPACHEscoreof25ormore GrowthFactors DespiteampleevidencethatgrowthfactorsacceleraterenalrecoveryinexperimentalARFintherat AstudyinalargeanimalmodelmorerepresentativeforhumanARFaswellasseveralclinicalstudiesincriticallyillpts nobeneficialorevendetrimentaleffects PotentialTreatmentsofARF Conclusion Severalresearchessuccessfulinunravelingthecomplexpathophysiologyofsepsis ARFdifferentpharmacologicinterventionsthatareeffectiveinamelioratingexperimentalARFfailedtocomeupwithatreatmentthatworksinhumans ThesuccessofactivatedproteinC byvirtueofitscombinedactionsontheinflammatory coagulation andfibrinolyticcascadesThecomplex multifactorialnatureofsepticARF requiremultitargetedinterventions DialyticTreatment IntermittentHemodialysis IHD VersusContinuousRenalReplacementTherapy CRRT ExtracorporealInflammatoryMediatorRemoval DialyticTreatment BenefitofCRRT betterhemodynamictolerance duetoamoregradualfluidandsoluteremoval Arandomizedcrossovertrialcompared24 hcontinuousarteriovenoushemofiltrationwitha24 hperiodencompassinga4 hIHDsessionin27criticallyillpatientsandfoundnodifferenceintheincidenceofBPdropsandvasopressorrequirements DialyticTreatment AlthoughphysiciansintuitivelypreferCRRTtoIHDincriticallyillptswithseverefluidoverloadandcardiovascularinstability Noconclusiveevidencetosupportthesuperiorityofeither